miRNA as therapeutic targets of pancreatic cancer

Coordinator:		Prof. Dr. med Stephan Hahn
Institution:		Ruhr-Universität Bochum, Molekulare Gastroenterologische Onkologie (MGO)
Homepage:		www.rub.de/mgo

Recently, microRNAs (miRNAs), a novel class of 18-23 nt long non-coding RNAs, have gained attention as another family of molecules involved in cancer development. Upon binding to their target RNAs, miRNAs cause posttranscriptional gene silencing by either cleaving the target mRNA or by inhibiting the translation process. Misregulation of miRNAs has been demonstrated in a number of hematological as well as solid tumor entities and is likely contributing to tumor development and progression. Due to their high stability even in poorly preserved specimen, miRNAs are expected to be robust clinical analytes, valuable for clinical research and biomarker discovery. By virtue of their apparent role in tumorigenesis, miRNAs may not only be potential targets for new prognostic and diagnostic strategies but also have therapeutic potential. A recent publication has shown that anti-miRNA oligonucleotides conjugated with cholesterol, also called antagomirs, are able to inhibit miRNA function in vivo in a mouse model system, indicating that therapeutic adjustment of miRNA over-expression in a given cancer type may become feasible. Similarly, it should be possible to correct miRNAs downregulated in tumors using miRNA expression strategies such as viral delivery systems.
Currently, miRNA suppression as a therapeutic option is hampered by stability, specificity, bioavailability and cellular uptake of miRNA knock-down compounds. In this TP we propose a novel approach to overcome two of the aforementioned problems. We aim at combining peptide nucleic acid (PNA) technology with its known superior stability and excellent sequence discrimination with tumor cell type specific uptake by coupling the PNA molecule with a receptor specific peptide.